title: Sugar receptor mediated drug delivery to macrophages in the therapy of experimental visceral leishmaniasis.
abstract: Methotrexate (MTX) conjugate of a neoglycoprotein, mannosyl bovine serum albumin, containing an average of 30 moles of MTX per mole of neoglycoprotein was taken up efficiently by murine peritoneal macrophages through cell surface mannosyl receptors. The conjugate strongly inhibits the growth of Leishmania donovani inside macrophages, with 50% inhibitory dose of 0.11 micrograms/ml MTX, which makes it 100 times more active than free MTX (50% inhibitory dose of 12.1 micrograms/ml). MTX conjugated to BSA or other non-specific neoglycoproteins like galactose-BSA and glucose-BSA have leishmanicidal effects comparable to free MTX. Moreover, in a murine model of experimental visceral leishmaniasis, the drug conjugate reduced the spleen parasite burden by more than 85% in a 30 day model whereas the same concentration of free drug caused little effect. The results demonstrate that neoglycoproteins may be useful as carriers for receptor mediated drug delivery to treat macrophage associated diseases.
authors.affiliation: Leishmania Group, Indian Institute of Chemical Biology, Calcutta.
authors.forename: P
authors.initials: P
authors.lastname: Chakraborty
authors.forename: A N
authors.initials: AN
authors.lastname: Bhaduri
authors.forename: P K
authors.initials: PK
authors.lastname: Das
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004337:Drug Carriers; D007700:Kinetics; D037181:Lectins, C-Type; D007893:Leishmania donovani / Q000187:drug effects / Q000254:growth & development*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology*; D008358:Mannose / Q000008:administration & dosage / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011485:Protein Binding; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000378:metabolism*; D012709:Serum Albumin; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D012709:Serum Albumin; C023840:mannose-bovine serum albumin conjugate; D012710:Serum Albumin, Bovine; D008358:Mannose; D008727:Methotrexate